A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns
Tekijät: Ciantar, Joanna; Marttila, Saara; Rajić, Sonja; Kostiniuk, Daria; Mishra, Pashupati P.; Lyytikäinen, Leo-Pekka; Mononen, Nina; Kleber, Marcus E.; März, Winfried; Kähönen, Mika; Raitakari, Olli; Lehtimäki, Terho; Raitoharju, Emma
Kustantaja: Taylor & Francis
Julkaisuvuosi: 2024
Journal: Epigenetics
Artikkelin numero: 2397297
Vuosikerta: 19
Numero: 1
ISSN: 1559-2294
eISSN: 1559-2308
DOI: https://doi.org/10.1080/15592294.2024.2397297
Verkko-osoite: https://doi.org/10.1080/15592294.2024.2397297
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/457754006
Eastern and Western Finns show a striking difference in coronary heart disease-related mortality; genetics is a known contributor for this discrepancy. Here, we discuss the potential role of DNA methylation in mediating the discrepancy in cardiometabolic disease-risk phenotypes between the sub-populations. We used data from the Young Finns Study (n = 969) to compare the genome-wide DNA methylation levels of East- and West-originating Finns. We identified 21 differentially methylated loci (FDR < 0.05; Δβ >2.5%) and 7 regions (smoothed FDR < 0.05; CpGs ≥ 5). Methylation at all loci and regions associates with genetic variants (p < 5 × 10−8). Independently of genetics, methylation at 11 loci and 4 regions associates with transcript expression, including genes encoding zinc finger proteins. Similarly, methylation at 5 loci and 4 regions associates with cardiometabolic disease-risk phenotypes including triglycerides, glucose, cholesterol, as well as insulin treatment. This analysis was also performed in LURIC (n = 2371), a German cardiovascular patient cohort, and results replicated for the association of methylation at cg26740318 and DMR_11p15 with diabetes-related phenotypes and methylation at DMR_22q13 with triglyceride levels. Our results indicate that DNA methylation differences between East and West Finns may have a functional role in mediating the cardiometabolic disease discrepancy between the sub-populations.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
JC was supported by funding from The Finnish Foundation for Cardiovascular Research, Yrjo Jahnsson Foundation and the Tampere City Science Fund. PPM was supported by the Academy of Finland (Grant number: 349708).The Young Finns Study has been financially supported by the Academy of Finland: grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrj\u00F6 Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation, Finnish Society of Clinical Chemistry, the Cancer Foundation Finland, and BETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117).The genome-wide methylation analyses in the LURIC cohort were financially supported by the German Federal Ministry for Education and Research (BMBF; grant agreement numbers 01EA1808A and 01EA1411A) within the framework of the German Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) (Halle-Jena-Leipzig).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
